A member of the OSCA/TMEM63 family of mechanosensitive calcium channels participates in cell wall integrity maintenance in Aspergillus nidulans.

The calF7 mutation in Aspergillus nidulans causes hypersensitivity to the cell wall compromising agents Calcofluor White (CFW) and Congo Red. In this research we demonstrate that the calF7 mutation resides in gene AN2880, encoding a predicted member of the OSCA/TMEM63 family of transmembrane glycoproteins. Those members of the family whose physiological functions have been investigated have been shown to act as mechanosensitive calcium transport channels. Deletion of AN2880 replicates the CFW hypersensitivity phenotype. Separately, we show that CFW hypersensitivity of calF deletion strains can be overcome by inclusion of elevated levels of extracellular calcium ions in the growth medium, and, correspondingly, wild type strains grown in media deficient in calcium ions are no longer resistant to CFW. These observations support a model in which accommodation to at least some forms of cell wall stress is mediated by a calcium ion signaling system in which the AN2880 gene product plays a role. The genetic lesion in calF7 is predicted to result in a glycine-to-arginine substitution at position 638 of the 945-residue CalF protein in a region of the RSN1_7TM domain that is highly conserved amongst filamentous fungi. Homology modeling predicts that the consequence of a G638R substitution is to structurally occlude the principal conductance pore in the protein. GFP-tagged wild type CalF localizes principally to the Spitzenkörper and the plasma membrane at growing tips and forming septa. However, both septation and hyphal morphology appear to be normal in calF7 and AN2880 deletion strains, indicating that any role played by CalF in normal hyphal growth and cytokinesis is dispensable.

Mental Health and Gender Affirmation of Black and Latine Transgender/Nonbinary Youth Compared to White Peers Prior to Hormone Initiation.

PURPOSE: To compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup. METHODS: Baseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study-a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure-Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups. RESULTS: The sample (mean age 16 years, range 12-20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p = .02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup. DISCUSSION: BLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms.

Comparing Substance Use and School-Based Stressors Among Black and Latinx Transgender Youth and Peers With Shared Minoritized Identities.

PURPOSE: The aim of this study is to compare substance use and school-based stressors among Black and Latinx transgender youth (trans BLY), White transgender youth (trans WY), and Black and Latinx cisgender youth (cis BLY) and identify associations between substance use and stressors among trans BLY. METHODS: We analyzed 2015-2017 Biennial California Healthy Kids Survey data with a weighted sample of the state's secondary school population. The analytic sample included 9th and 11th grade trans BLY, trans WY, and cis BLY. Past 30-day and lifetime substance use (cigarettes, e-cigarettes/vaping, marijuana, and alcohol) and school-based stressors (victimization, race-, gender-, and sexuality-based harassment) were compared between cohorts via logistic regression. For trans BLY, associations between substance use and stressors were assessed via logistic regression. RESULTS: The analytic sample (n = 19,780) included 252 trans BLY, 104 trans WY, and 19,424 cis BLY. Among trans BLY, estimated prevalence of 30-day (and lifetime) use of cigarettes, e-cigarette/vaping, marijuana, and alcohol were 13% (23%), 19% (39%), 27% (42%), and 29% (48%), respectively. Trans BLY had similar odds of 30-day and lifetime use of all substances compared to trans WY but higher odds of use compared to cis BLY. For trans BLY, race- and gender-based harassment and higher victimization levels were associated with higher odds of 30-day and lifetime use of all substances. Sexuality-based harassment was associated with higher odds of 30-day and lifetime marijuana and alcohol use. DISCUSSION: Trans BLY have high prevalence of substance use, comparable with trans WY but higher than cis BLY. Substance use among trans BLY is associated with school-based stressors.

Transgender and other gender diverse adolescents with eating disorders requiring medical stabilization.

BACKGROUND: Despite the high prevalence of eating disorders in gender diverse adolescents, little is known about the characteristics of gender diverse youth with eating disorders who require inpatient medical stabilization. The primary objective of this study was to describe the medical, anthropometric, and psychiatric characteristics of gender diverse adolescents hospitalized for eating disorders and compare these characteristics to cisgender peers hospitalized for eating disorders. The secondary objective was to evaluate percent median body mass index as one marker of malnutrition and treatment goal body mass index as a recovery metric between patients' birth-assigned sex and affirmed gender using standardized clinical growth charts. METHODS: A retrospective chart review was conducted of 463 patients admitted to an inpatient eating disorders medical unit between 2012 and 2020. To compare medical, anthropometric, and psychiatric data between gender diverse and cisgender patients, chi-square/Fisher's exact and t-tests were used. Clinical growth charts matching the patients' birth-assigned sex and affirmed gender identity were used to assess percent of median body mass index and treatment goal body mass index. RESULTS: Ten patients (2.2%) identified as gender diverse and were younger than cisgender patients [13.6 (1.5) years vs. 15.6 (2.7) years, p = 0.017]. Gender diverse patients were hospitalized with a higher percent median body mass index compared to cisgender peers [97.1% (14.8) vs. 87.9% (13.7), p = 0.037], yet demonstrated equally severe vital sign instability such as bradycardia [44 (8.8) beats per minute vs. 46 (10.6) beats per minute, p = 0.501], systolic hypotension [84 (7.1) mmHg vs. 84 (9.7) mmHg, p = 0.995], and diastolic hypotension [46 (5.8) mmHg vs. 45 (7.3) mmHg, p = 0.884]. Gender diverse patients had a higher prevalence of reported anxiety symptoms compared to cisgender patients (60% vs. 28%, p = 0.037). CONCLUSIONS: Gender diverse patients demonstrated complications of malnutrition including vital sign instability despite presenting with a higher weight. This is consistent with a greater proportion of gender diverse patients diagnosed with atypical anorexia nervosa compared to cisgender peers. Additionally, psychiatric comorbidities were present among both groups, with a larger percentage of gender diverse patients endorsing anxiety compared to cisgender patients.

Gender diverse is a term that includes gender identities such as (but not limited to) transgender, non-binary, and gender fluid. Eating disorders are becoming increasingly recognized among this population. In recent years there has been a better understanding of the risk factors and screening for eating disorders in the outpatient setting for gender diverse adolescents. However, the medical, anthropometric, and psychiatric characteristics of gender diverse adolescents with eating disorders requiring inpatient medical stabilization are poorly understood. This study examines these characteristics in gender diverse adolescents hospitalized for eating disorder-related medical complications from 2012 to 2020. Gender diverse adolescents presented for medical hospitalization with signs of malnutrition, including vital sign instability and laboratory abnormalities, as well as additional psychiatric diagnoses such as depression and anxiety. Understanding the medical, anthropometric, and psychiatric presentation of this population can lead to more tailored and comprehensive care with the potential to reduce the risks of adverse health outcomes.

Using Standardized Patients to Augment Communication Skills and Self-Efficacy in Caring for Transgender Youth.

OBJECTIVE: To examine the impact of standardized patient encounters (SPEs) on gender-affirming communication skills and self-efficacy of pediatrics learners. METHODS: Fourth-year medical students, pediatrics interns, psychiatry interns, and nurse practitioner trainees on 1-month adolescent medicine blocks completed a curriculum with e-learning activities that was expanded to include SPEs. Following e-learning, learners completed 2 SPEs featuring transgender adolescent cases. Faculty observers and standardized patients completed checklists focused on history-taking, counseling, and interpersonal communication, and provided learner feedback after each case. The curriculum was evaluated by comparing skills checklists scores from case 1 to case 2 via Wilcoxon signed-rank tests. Self-efficacy was assessed precurriculum (Assessment 1), post-e-learning (Assessment 2), and post-SPE (Assessment 3) using a previously developed instrument. Changes in self-efficacy scores were assessed via linear regression models with generalized estimating equations. RESULTS: Forty-three eligible learners participated in the study. The majority were pediatrics interns, and 5 learners had worked in a transgender clinic prior to the curriculum participation. Learners increased median total checklist scores between cases from 22 to 28 (P < .001) (maximum score of 34). Learners' overall self-efficacy scores improved by 3.4 (confidence interval [CI]: 2.9-3.9; P < .001) between Assessments 1 and 2 and by 1.5 (CI: 1.2-1.7; P < .001) from Assessment 2 to 3. Similar improvements in checklist scores and self-efficacy occurred within stratified learner types. CONCLUSIONS: The combination of SPEs with e-learning is effective at improving self-efficacy and gender-affirming communication skills for a multidisciplinary pediatrics learners. The comprehensive curriculum allowed learners inexperienced with transgender youth to apply knowledge and practice skills.

Disordered Eating, Body Image Dissatisfaction, and Associated Healthcare Utilization Patterns for Sexual Minority Youth.

PURPOSE: To determine the prevalence of disordered eating behaviors (DEBs) and body image dissatisfaction (BID) according to sexual minority youth (SMY) status and describe healthcare utilization patterns by SMY status. METHODS: Retrospective data from 107,528 adolescents, who had a Well Check in Kaiser Permanente Northern California in 2016, were used to compare DEB and BID by SMY status. Multivariate logistic models were used to examine the associations of SMY, birth-assigned sex, age, race/ethnicity, and body mass index on DEB and BID. The utilization of specialized eating disorder (ED) medical and mental health services and general mental health services was described at one Kaiser Permanente Northern California facility. RESULTS: BID was reported in 20,763 (19.3%) adolescents, DEB in 1,458 (1.7%) adolescents, and 5,363 (5%) adolescents identified as SMY. SMY had higher odds of having DEB and BID than non-SMY, respectively (adjusted odds ratio 2.0 95% confidence interval [1.9-2.2] and adjusted odds ratio 3.8 [3.4-4.2]). Regardless of SMY status, adolescents with older age, female sex, nonwhite race, and elevated body mass index had higher odds of ED risk factors. SMY with ED risk factors had higher ED medical utilization than non-SMY with ED risk factors (4.6% vs. 1.6%). However, SMY status was not associated with utilization of specialized ED mental health services. CONCLUSIONS: SMY had increased rates of DEB and BID but had underutilization of specialized ED mental health services. Future targeted efforts to prevent eating disorder-related mortality and morbidity for SMY should include targeted eating disorder screening and referral to specialized ED medical and mental health services.

Mental Health and Psychosocial Risk and Protective Factors Among Black and Latinx Transgender Youth Compared With Peers.

Importance: Black and Latinx transgender youth experience stigma that may increase their susceptibility to mental health symptoms. Objective: To compare past-year mental health symptoms and psychosocial factors among Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth. Design, Setting, and Participants: This survey study used data from the 2015-2017 Biennial California Healthy Kids Survey with a weighted sample (N = 45 269) representative of California's secondary school population. The analytic sample (n = 19 780) included Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth in the 9th and 11th grades. Data analysis was conducted from July 2020 to February 2021. Main Outcomes and Measures: Outcomes include past-year depressive symptoms and suicidality. Psychosocial risk factors include school-based victimization, gender-based harassment, sexuality-based harassment, and race-based harassment; protective factors include school connectedness and caring adult relationships. Results: The analytic sample of 19 780 participants (in 9th grade: weighted percentage, 51% [95% CI, 50% to 52%]; female participants: weighted percentage, 50% [95% CI, 49% to 51%]) included 252 Black and Latinx transgender youth (weighted percentage, 1.3% [95% CI, 1.1% to 1.5%]), 104 White transgender youth (weighted percentage, 0.7% [95% CI, 0.6% to 0.8%]), and 19 424 Black and Latinx cisgender youth (weighted percentage, 98.0% [95% CI, 97.8% to 98.2%]). For Black and Latinx transgender youth, estimated prevalence of depressive symptoms and suicidality were 50% (95% CI, 44% to 57%) and 46% (95% CI, 39% to 52%), respectively. Logistic regression models adjusted for grade, living arrangement, and reported sex indicated that compared with White transgender youth, Black and Latinx transgender youth had similar odds of depressive symptoms (adjusted odds ratio, 0.6; 95% CI, 0.4 to 1.1) and suicidality (adjusted odds ratio, 1.1; 95% CI, 0.6 to 1.8) and similar odds of all forms of harassment (eg, race-based harassment: adjusted odds ratio, 1.5; 95% CI, 0.8 to 2.6). Regression models indicated that compared with White transgender youth, Black and Latinx transgender youth had similar levels of victimization (adjusted linear regression coefficient, 0.5; 95% CI, -0.3 to 1.3) and caring adult relationships (adjusted linear regression coefficient, -0.6; 95% CI, -1.4 to 0.09) but lower levels of school connectedness (adjusted linear regression coefficient, -1.6; 95% CI, -2.9 to -0.4). With similar analyses, compared with Black and Latinx cisgender youth, Black and Latinx transgender youth had higher odds of depressive symptoms (adjusted odds ratio, 2.7; 95% CI, 2.0 to 3.7) and suicidality (adjusted odds ratio, 5.9; 95% CI, 4.3 to 8.0), higher odds and levels of all forms of harassment and victimization (eg, race-based harassment: adjusted odds ratio, 3.2; 95% CI, 2.4 to 4.5), and lower levels of school connectedness (adjusted linear regression coefficient, -2.6; 95% CI -3.3 to -1.8) and caring adult relationships (adjusted linear regression coefficient, -0.9; 95% CI -1.3 to -0.5). Conclusions and Relevance: In this study, Black and Latinx transgender youth had high rates of mental health symptoms, with rates comparable with White transgender youth but higher than Black and Latinx cisgender youth. Their unique pattern of psychosocial risk and protective factors for these mental health symptoms should be factored in clinical preventive services and school-based interventions to support them.

A Pediatric Transgender Medicine Curriculum for Multidisciplinary Trainees.

Introduction: While pediatricians should receive training in the care of transgender youth, a paucity of formal educational curricula have been developed to train learners to care for this vulnerable population. Methods: We developed a curriculum including six online modules and an in-person afternoon session observing clinic visits in a pediatric gender clinic. Learners-fourth-year medical students, interns, and nurse practitioner trainees-received protected time during an adolescent medicine rotation to complete the online modules (total duration: 77 minutes). For 20 learners, we assessed the impact of the entire curriculum-online modules and in-person observation-on self-perceived knowledge of considerations for transgender youth. For 31 learners, we assessed the effect of the online modules alone on knowledge and self-efficacy. Descriptive analyses illustrated changes in educational domains by learner group. Results: On evaluations of the entire curriculum (modules and observation), median self-perceived knowledge scores (1 = not at all knowledgeable/aware, 5 = extremely knowledgeable/aware) increased within learner groups: pediatric interns (from 2.3 to 4.0), nurse practitioner trainees (from 2.9 to 4.7), fourth-year medical students (from 3.3 to 4.9), and psychiatry interns (from 2.8 to 4.4). Assessment of learners completing only the online modules demonstrated increases in median knowledge and self-efficacy scores within learner groups. All learner groups highly valued the curriculum. Discussion: Our curriculum for multidisciplinary learners in the care of transgender youth was successful and well received. Increasing learner knowledge and self-efficacy is an important step towards skill development in patient care for the transgender youth population.

Identification of Sexual Minority Youth in Pediatric Primary Care Settings Within a Large Integrated Healthcare System Using Electronic Health Records.

PURPOSE: The aim of the study was to estimate the prevalence of sexual minority youth (SMY) within an integrated health care system using a standardized questionnaire. METHODS: This study assessed SMY status in youth aged 12.5-18 years using a previsit Well Check questionnaire at Kaiser Permanente Northern California facilities in 2016. SMY was defined as self-reported attraction to the same sex or both sexes. RESULTS: A total of 93,817 youth (87.3%) self-reported sexual attraction, and 5% (n = 5,329) of respondents (N = 107,532) identified as SMY: 1.7% were attracted to same sex, and 3.2% were attracted to both sexes. There were youth who responded neither (1.5%) and unsure (2.4%). Females were 2.8 times (95% confidence interval 2.6-2.94) more likely to be SMY than males. SMY status significantly increased with age. Nonwhite youth were significantly less likely to be SMY compared with white youth. CONCLUSIONS: This is the first study to examine SMY prevalence in pediatric primary care. Primary care providers can use previsit screening before preventive visits to identify and support sexual minority adolescents, facilitate family acceptance, and promote healthy behaviors with care coordination.

Experiences With Querying Gender Identity Across Seven Adolescent Medicine Sites.

PURPOSE: To determine how the seven Maternal and Child Health Bureau funded Leadership and Education in Adolescent Health (LEAH) programs currently obtain information on gender identity from their patients. METHODS: A computerized survey was sent to all LEAH site directors with questions to identify if and how programs documented youth's gender identity and barriers to implementation. RESULTS: With response rate of 100%, seven LEAH programs reported a total of 43 primary care and specialty clinics. For clinics with Electronic Health Records, 67% of clinics had a standardized gender identity question. Barriers to implementing a standardized question included concerns about confidentiality, lack of trained providers, low numbers of transgender patients, and no validated gender identity question. CONCLUSIONS: Incorporation of inquiry of gender identity is possible in numerous clinical settings that serve adolescents. Future research is needed to determine how this information affects conversations with providers and necessary referrals to treatment.

Teaching paediatric transgender care.

BACKGROUND: We aimed to evaluate the effect of online modules - as stand-alone training - on paediatric transgender-related self-perceived knowledge, objective knowledge, and clinical self-efficacy of learners. We previously evaluated the online modules as part of a larger curriculum that included observation in a paediatric transgender clinic, and assessed change in self-perceived knowledge. METHODS: Paediatric interns, psychiatry interns, fourth-year medical students and nurse practitioner students were administered assessments before and after the completion of six online modules focused on medical and psychosocial considerations for transgender youth. The assessments queried learner demographics and transgender clinical exposure. Nine items tested transgender-related objective knowledge. Twenty-four items asked learners to rate self-perceived transgender-specific knowledge (1, not at all knowledgeable; 5, completely knowledgeable). Thirteen self-efficacy items asked learners to rate confidence in their ability to evaluate and counsel these youth (0, not at all confident; 10, completely confident). Overall and subscores were calculated for each domain. Wilcoxon signed-rank tests were used to compare the pre- and post-module scores. RESULTS: Thirty-six learners were eligible to join the study and 86% (n = 31) participated. Among the participants, 90% (n = 28) completed both assessments. The median number of transgender patients seen before the curriculum was one, and 10% had past experience in a transgender clinic. Comparing pre- and post-module scores, the overall objective knowledge scores increased from 22 to 56% (p < 0.001), self-perceived knowledge scores increased from 1.8 to 3.8 (p < 0.001) and self-efficacy scores increased from 3.5 to 7.0 (p < 0.001). [What is] the effect of online modules on paediatric transgender-related self-perceived knowledge [?] DISCUSSION: This study suggests that e-learning was an effective stand-alone intervention to enhance transgender-related knowledge and self-efficacy in interdisciplinary learners.

Enhancing Pediatric Trainees' and Students' Knowledge in Providing Care to Transgender Youth.

PURPOSE: To enhance pediatric trainees' and students' knowledge of the psychosocial and medical issues facing transgender youth through a comprehensive curriculum. METHODS: During the 2015-2016 academic year, we administered a transgender youth curriculum to fourth-year medical students, pediatric interns, psychiatry interns, and nurse practitioner students on their 1-month adolescent and young adult medicine rotation. The curriculum included six interactive, online modules and an observational experience in a multidisciplinary pediatric gender clinic. The online modules had a primary care focus with topics of general transgender terminology, taking a gender history, taking a psychosocial history, performing a sensitive physical examination, and formulating an assessment, psychosocial plan, and medical plan. At the completion of the curriculum, learners completed an evaluation that assessed change in perceived awareness and knowledge of transgender-related issues and learner satisfaction with the curriculum. RESULTS: Twenty learners participated in the curriculum with 100% completing the curriculum evaluations, 100% reporting completing all six online modules, and 90% attending the gender clinic. Learners demonstrated a statistically significant improvement in all pre-post knowledge/awareness measures. On a Likert scale where 5 indicated very satisfied, learners' mean rating of the quality of the curriculum was 4.5 ± .7; quality of the modules was 4.4 ± .7; and satisfaction with the observational experience was 4.5 ± .8. CONCLUSIONS: A comprehensive curriculum comprised interactive online modules and an observational experience in a pediatric gender clinic was effective at improving pediatric learners' perceived knowledge of the medical and psychosocial issues facing transgender youth. Learners also highly valued the curriculum.

Documentation of Gender Identity in an Adolescent and Young Adult Clinic.

PURPOSE: To determine if changing electronic health record (EHR) note templates can increase documentation of gender identity in an adolescent and young adult clinic. METHODS: A two-step gender question was added to EHR note templates for physicals in February 2016. A retrospective chart review was performed 3 months before and after this addition. The primary measure was whether answers to the two-step question were documented. Gender identity/birth-assigned sex discordance, age, and use of the appropriate note template post-template change were also measured. RESULTS: One hundred twenty-five pretemplate change and 106 post-template change physicals were reviewed with an inter-rater reliability of 97%. Documentation of answers to the two-step gender identity question increased from 11% to 84% (p < .001). CONCLUSIONS: This study suggests that incorporating a standardized question into EHR note templates is effective at improving the documentation of gender identity in youth presenting for annual physicals.